Pallister-Hall syndrome (Hall-Palister syndrome, hypothalamic hamatoblastoma syndrome) is an extremely rare congenital disorder in which a patient has abnormalities of the genitals and urinary tract, face, brain and skeleton, although other symptoms also occur. The doctor treats the presenting symptoms symptomatically. Most patients with Pallister-Hall syndrome have mild symptoms, making the prognosis good. Only occasionally are the prospects less good because serious complications arise, for example in the anus or airways. Hall et al. first reported the disease in the medical literature in 1980 and in 1989 the doctor Pallister described several more patients.

• Epidemiology of congenital disorder
• Causes
• Symptoms
• Diagnosis and examinations
• Treatment of abnormalities
• Prognosis of Pallister-Hall syndrome
• Complications of hereditary disease

Epidemiology of congenital disorder

Since the condition was described, about a hundred patients have been reported in the medical literature. The prevalence is probably 1 in 100,000 to 1 in 1,000,000. Patients with mild symptoms are often not diagnosed with the disease.

Causes

Pallister-Hall syndrome is the result of mutations (changes) in the GLI3 gene (7p13). This affects the development of various body parts. Pallister-Hall syndrome has an autosomal dominant inheritance pattern. A parent passes this on to offspring in 50% of cases, but the expression is highly variable. In addition, the condition often arises as a result of de novo (new) mutations.

Symptoms

The clinical presentation of Pallister-Hall syndrome is highly variable, although similarities are often present within the same family.

Endocrine

A hypothalamic hamartoma (benign tumor) is often present but does not cause symptoms. This symptom is associated with panhypopituitarism (lack of all hormones secreted by the pituitary gland). Acute primary adrenal insufficiency also occurs in patients with severe symptoms, as do milder forms of adrenal insufficiency. Some patients experience early puberty.

Genitals and urinary system

Absent kidneys or no proper abnormality of the kidney and other genitourinary abnormalities occur, such as vaginal atresia or hydrometrocolpos, microphallus, cryptorchidism (undescended testes in boys) and an imperforate anus (absent defecation hole).

Sight

With this congenital condition, the patient has typical facial abnormalities such as a short nose, a flat nasal bridge and low-set, backward-curved ears. A cleft palate (cleft), a cleft uvula and multiple buccal frenula (tongue ties) also occur. Furthermore, many patients have a cleft epiglottis (malformation of the airways) which is not accompanied by any signs. However, some patients present with a more severe posterior laryngeal fissure that sometimes leads to fatal respiratory failure.

Brain

Neurological signs also occur such as gelastic epilepsy (seizures manifesting as grimacing on faces, smiling or laughing) or other types of seizures.

Skeleton

Most patients with Pallister-Hall syndrome already suffer from skeletal abnormalities such as polydactyly (extra fingers and/or toes) at birth. This finger and/or toe abnormality is sometimes accompanied by syndactyly (fusion of fingers and/or toes) of the skin and nail abnormalities. Furthermore, the patient sometimes presents with generalized skeletal dysplasia with mesomelic shortening and radial bowing of limbs.

Other symptoms

Other symptoms include:

• congenital heart defects (see this term).
• abnormal lung lobation
• intrauterine growth retardation (slowing of growth in the uterus)

Diagnosis and examinations

Physical and diagnostic examination

The doctor performs an MRI scan to detect brain abnormalities. An X-ray reveals any skeletal abnormalities. Furthermore, it is possible to perform a genetic test that confirms the condition. An ultrasound of the kidneys is also necessary. The patient also receives a blood test that reveals any abnormalities.

Differential diagnosis

Differential diagnoses include:

• Bardet-Biedl syndrome (skeletal, facial and ocular symptoms)
• congenital hypothalamic hamartoma syndrome
• craniopharyngioma (benign brain tumor of the pituitary gland)
• Ellis Van Creveld syndrome (bone disorder)
• Greig cephalopolysyndactyly syndrome (abnormalities of the head, fingers and toes)
• Holt-Oram syndrome (skeletal and heart abnormalities)
• Holzgreve-Wagner-Rehder syndrome
• McKusick-Kaufman syndrome
• oral-facial-digital syndrome type 6
• Smith-Lemli-Opitz syndrome

Treatment of abnormalities

The treatment of patients with Pallister-Hall syndrome is symptomatic and supportive. At birth, the doctor monitors the breathing of patients and also performs an indirect laryngoscopy (internal inspection of the throat, larynx and vocal cords). Sometimes a tracheotomy is required to improve breathing. Patients with an imperforate anus (non-perforated anus) undergo surgery to correct this problem. Furthermore, patients require multiple lifelong hormone replacement therapies.

Prognosis of Pallister-Hall syndrome

The majority of patients have a good prognosis as the abnormalities are not life-threatening. The majority of patients also have normal intelligence and no behavioral changes. The majority of patients also have mild symptoms. Only a small percentage of patients have serious complications.

Complications of hereditary disease

In many cases, the growths in the brain do not cause health problems, but some hypothalamic hamartomas do lead to seizures or hormone abnormalities that are life-threatening in childhood. Occasionally, patients suffer from a severe form of the syndrome, causing airway malformations that are sometimes fatal. An imperforate anus is also fatal if the doctor does not recognize it in time.